Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF-κB dependant TGF-β activation: A biphasic experimental study

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating and fatal lung disorder with high mortality rate. Unfortunately, to date the treatment for IPF remains unsatisfying and in severe cases lung transplantations are performed as a therapeutic measure. Thus, it becomes great interest to find novel agents to treat IPF. Berberine, a plant alkaloid known for its broad pharmacological activities remains a remedy against multiple diseases. This study was hypothesized to investigate the antifibrotic potential of berberine against bleomycin-induced lung injury and fibrosis, a tentative animal model. Male wistar rats were subjected to single intratracheal instillation of 2.5U/kg of bleomycin on day 0. Berberine treatments were either provided in preventive or therapeutic mode respectively. Berberine administration significantly ameliorated the bleomycin mediated histological alterations and reduced the inflammatory cell infiltrate in BALF. Berberine significantly blocked collagen accumulations with parallel reduction in the hydroxyproline level. The immunological sign of bleomycin stimulated mast cell deposition and histamine release were considerably reduced by berberine. Berberine enhanced the antioxidant status, through upregulating the redox sensing transcription factor nuclear factor E2-related factor 2 (Nrf2). Berberine inhibited the bleomycin mediated activation of inflammatory mediator nuclear factor kappa B (NF-κB) and suppressed its downstream target inducible nitric oxide synthase (iNOS). Strikingly, berberine exhibited target attenuation of tumor necrosis factor alpha (TNF-α) and key pro-fibrotic mediator, transforming growth factor beta 1 (TGF-β1). Taken together, this study reveals the beneficial effects of berberine against bleomycin mediated fibrotic challenge through activating Nrf2 and suppressing NF-κB dependent inflammatory and TGF-β1 mediated fibrotic events.